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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of our study was to examine the release of various lipid and peptide contracting autacoids by aortae of normal and atherosclerotic rabbits. Leukotriene (LT) E4, an enzymatic derivative of LTC4, thromboxane (Tx) B2, and endothelin-1 (ET-1) were measured by radioimmunoassay techniques in aortic preparations of normal and cholesterol-fed rabbits. Intact aortae of normal rabbits incubated with the calcium ionophore A23187 for 1 h at 37 degrees C released LTE4 and TxB2 (22 +/- 3.5 and 14.8 +/- 2 pg/mg of tissue, respectively, mean +/- SEM, n = 33). Removal of aortic endothelium was associated with a significant reduction in LTE4 (44%) and TxB2 (58%) release. In aortic preparations from cholesterol-fed rabbits, the release of LTE4 was significantly enhanced (41 +/- 8 pg/mg of tissue, mean +/- SEM, n = 27) whereas TxB2 was not significantly altered. No detectable amounts of ET-1 were measured after 1 h of incubation. However, at 4 h, an endothelium-dependent release of ET-1 from normal aortae was demonstrated. In atherosclerotic aortae, ET-1 release was significantly higher than in controls (10 +/- 1.3 vs. 5 +/- 0.5 pg/cm2, mean +/- SEM, n = 16). We conclude that enhanced formation of vasoconstrictor autacoids may contribute to altered vasomotion of atherosclerotic blood vessels.
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PMID:Release of contracting autacoids by aortae of normal and atherosclerotic rabbits. 128 72

We studied whether endothelin-1 (ET-1) would affect its own synthesis. Human umbilical cord vein endothelial cells in methionine-poor culture medium containing [35S] methionine were treated with synthetic ET-1 or ET-3. Immunoprecipitation of 35 S-labeled ET-1 was performed with rabbit ET-1 antiserum. ET-1 caused an 40 +/- 4% (mean +/- SEM) increase of immunoprecipitable 35 S-labeled ET-1 as confirmed by its elution point in reversed phase high power liquid chromatography (HPLC). ET-3 caused a 23 +/- 2% increase in ET-1 concentration. Amplification of cDNA by PCR showed both ET-1 and ETB receptor mRNAs in human cord vein endothelial cells. We conclude that ET-1 increases its own synthesis in endothelial cells. This suggests a positive autocrine feed-back action of ET-1 on its own synthesis, an effect which is probably mediated by non-specific ETB receptors.
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PMID:Endothelin-1 stimulates its own synthesis in human endothelial cells. 141 49

The remodeling of pulmonary vessels that occurs in association with pulmonary hypertension involves, in part, thickening of the adventitia. The stimulus for this process is not understood. One explanation is that endothelial cells secrete a growth factor that expands the local population of fibroblasts by acting as a chemoattractant and mitogen. Endothelins are a family of potent newly discovered vasoactive peptides. One of these compounds, endothelin-1 (ET-1), is secreted by endothelial cells and is known to constrict pulmonary vessels. Another, endothelin-3 (ET-3), is not secreted by endothelial cells and is less potent as a pulmonary vasoconstrictor. We hypothesized that the endothelins may have the capacity both to constrict these vessels and to initiate fibroblast chemotaxis and replication. Here we investigated the effects of both ET-1 and ET-3 on the chemotaxis and replication of fibroblasts derived from pulmonary vessels. Cells were isolated from rat pulmonary arteries, cultured in medium and 10% newborn calf serum, and used between passages 2 and 5. Chemotaxis was assessed using a modified Boyden chamber with a polycarbonate filter (pore size, 8 microns) separating cells in the upper chambers from endothelin in the lower chambers. Replication was assessed both by direct cell counts and by a colorimetric assay based on uptake and subsequent release of methylene blue. Both ET-1 and ET-3 induced chemotaxis of pulmonary artery fibroblasts and did so in a dose-dependent fashion. The maxima for both peptides occurred at a concentration of about 10(-7) M, when chemotaxis was greatest for ET-1 (22 +/- 1.4 versus 14 +/- 1.8 cells/grid [mean +/- SEM], (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelin-1 and endothelin-3 induce chemotaxis and replication of pulmonary artery fibroblasts. 141 25

Endothelin-1, a potent vasoconstrictor, has been reported to stimulate mitogenesis in various types of normal and neoplastic cells and to be involved in neurotransmission. Recently, many human cancer cell lines, including those from the human colon, have been shown to produce endothelin. In this study, the occurrence of endothelin-1 binding sites was investigated in human colonic cancer tissues using in vitro autoradiography. Specific [125I]endothelin-1 binding sites were identified over tumour vessels and stromal tissues surrounding cancer cell nests. The distribution was heterogeneous, and dense silver grains were localized, especially over clusters of fibroblasts adjacent to the cancer cell nests. Endothelin binding was minimal in the cancer cells, as in the normal crypt epithelium. Quantitative analysis of the autoradiographs demonstrated high affinity (Kd = 0.50 +/- 0.06 nM; mean +/- SEM) binding sites, with a maximum binding capacity (Bmax) of 40 +/- 3.2 amol/mm2 in the cancer tissues. Our results provide evidence that specific endothelin-1 binding sites are expressed in the stromal tissues including tumour vessels, fibroblasts, and nerve fibres. Endothelin-1 may play a modulatory role in blood supply, mitogenesis, and neurotransmission in a paracrine fashion through the stromal components in human colonic cancers.
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PMID:Autoradiographic localization of endothelin-1 binding sites in human colonic cancer tissue. 146 5

An intravital fluorescence microscope system was used to investigate the pharmacological effects of endothelin-1 (ET-1) on the coronary microcirculation in the isolated beating hearts of rats. The heart was perfused by retrograde aortic steady flow with an oxygenated Krebs-Ringer solution containing FITC-dextran. Changes in diameters of coronary microvessels accompanying the cumulative injection of ET-1 in the perfusate were observed and recorded with a video camera system. Coronary perfusion pressure was also measured during each experiment. Bolus injections of ET-1 (1-300 pmole) elicited a dose-dependent increase in perfusion pressure from 54 +/- 6 mm Hg (mean +/- SEM; n = 10, before the ET-1 injection) to 144 +/- 9 mm Hg (n = 8, at the ET-1 dose of 300 pmole). A dose-dependent narrowing of microvessels was also observed. This vasoconstriction was especially prominent in small-sized arterioles; the maximum vasoconstriction of the smaller arterioles was significantly higher than that of the larger arterioles (P less than 0.05). The response induced by ET-1 dose of 3-10 pmole was significantly larger in arterioles than in postcapillary venules in the diameter range between 10 and 40 microns. The vasoconstriction produced by ET-1 was inhomogeneous. Some part of bifurcations of arterioles showed a prominent localized vasoconstriction, and occasionally showed a complete luminal obstruction. Such a segmental vasospasm might be attributed to localized sensitivities of arterioles to ET-1. These findings suggest that ET-1 may have an important role in governing the coronary resistance and regulating the capillary flow in the myocardium.
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PMID:Vasoconstrictor effects of endothelin-1 on myocardium microcirculation studied by the Langendorff perfusion method: differential sensitivities among microvessels. 158 62

Endothelin-1 is a 21 amino acid peptide originally isolated from porcine aortic endothelium and has recently been localized within the central nervous system. We have administered endothelin-1 in a dynamic perfusion system in order to study its possible effects on the rat hypothalamus and anterior pituitary. Tissue (hypothalami or quartered pituitaries) was placed into plastic chambers and was perfused with oxygenated Krebs-bicarbonate solution. After an interval to establish stable basal peptide release, endothelin-1 was administered at two doses (0.1 and 1 microM) and the release of substance P, vasoactive intestinal peptide, 7B2, and somatostatin was measured, the last being detectable only in hypothalamic perfusates. Both concentrations of endothelin-1 led to a significant increase (P less than 0.01) in the release of substance P from the hypothalamus and pituitary, but not of vasoactive intestinal peptide, 7B2, or somatostatin. Thus after the 0.1 microM and 1 microM endothelin-1 perfusion substance P release from the hypothalamus increased by 125 +/- 5% and 215 +/- 15% (mean +/- SEM) of basal and from the pituitary by 168 +/- 8% and 276 +/- 15% (mean +/- SEM). No change occurred in the output of ACTH or other pituitary hormones. The release of substance P from hypothalamus or pituitary after stimulation with endothelin-1 was not blocked when a calcium free medium was used. Endothelin-1 binding sites were identified on rat pituitary cell membranes. These findings suggest the possibility that endothelin may act as a paracrine substance, neurotransmitter, or neuromodulator in the hypothalamo-pituitary axis.
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PMID:Release of substance P from rat hypothalamus and pituitary by endothelin. 169 95

An intravital fluorescence videomicroscope system was used to investigate the pharmacological effects of endothelin-1 (ET-1) on the coronary microcirculation in isolated beating hearts of rats. The heart was perfused by retrograde aortic steady flow with an oxygenated Krebs-Ringer solution containing FITC-dextran. Cumulative injections of ET-1 (1-30 pmol) elicited a dose-dependent increase in perfusion pressure from 52 +/- 15 mm Hg (mean +/- SEM; n = 6) before the ET-1 injection to 104 +/- 23 mm Hg at the ET-1 dose of 30 pmol. A dose-dependent narrowing of microvessels was also observed on a monitor screen. This diffuse vasoconstriction was especially prominent in small arterioles; the maximum vasoconstriction of the smaller arterioles was significantly higher than that of the larger arterioles. These findings suggest that ET-1 may have an important role in governing the coronary resistance and regulating the capillary flow in myocardium.
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PMID:Effects of endothelin-1 on coronary microcirculation in isolated beating hearts of rats. 172 54

Responses of blood pressure to intravenous (i.v.) or intracerebroventricular (i.c.v.) endothelin-1 (ET-1) in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were investigated. Conscious male SHRs and WKY rats were used for the experiments. ET-1 (300-1,000 ng/kg) was injected intravenously in the i.v. experiments, or 30 and 100 ng/kg of ET-1 were injected into the lateral ventricle in the i.c.v. experiments. The initial depressor response to i.v. ET-1 was greater in SHRs (n = 10) than in WKY rats (n = 10) at 1,000 ng/kg (-54 +/- 6 vs. -41 +/- 3 mm Hg, mean +/- SEM, p less than 0.05). The subsequent pressor response to i.v. ET-1 was smaller in SHRs than in WKY rats (3.5 +/- 0.8 vs. 7.0 +/- 0.9 mm Hg at 300 ng/kg, p less than 0.05, and 11 +/- 2 vs. 17 +/- 2 mm Hg at 1,000 ng/kg, p less than 0.05). Pressor responses to i.c.v. ET-1 were not different in SHRs (n = 8) and WKY rats (n = 8) at both doses (10 +/- 4 vs. 10 +/- 3 mm Hg at 30 ng/kg, and 46 +/- 10 vs. 49 +/- 10 mm Hg at 100 ng/kg). A greater initial depressor response and a smaller subsequent pressor response to i.v. ET-1 were observed in SHRs than in WKY rats. The attenuated pressor response to intravenously administered ET-1 may be unique since vasoconstrictor responses to other known vasoactive substances such as angiotensin, catecholamines, or vasopressin are reportedly augmented in SHRs. We did not find any difference in responsiveness to i.c.v. ET-1 between SHRs and WKY rats.
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PMID:Blood pressure responses to intravenous or intracerebroventricular endothelin-1 in spontaneously hypertensive rats. 172 61

Using a highly sensitive radioimmunoassay, elevated plasma immunoreactive endothelin (ir-ET) levels were found in patients with diabetes mellitus (1.88 +/- 0.12 pmol/L, mean +/- SEM, n = 100), patients undergoing maintenance hemodialysis (4.28 +/- 0.76 pmol/L, n = 14), patients with acute myocardial infarction (3.43 +/- 1.03 pmol/L, n = 6), and patients with subarachnoid hemorrhage (4.92 +/- 0.64 pmol/L, n = 14) (normal controls: 0.54 +/- 0.05 pmol/L, n = 19). ir-ET was also present in urine (2.1 +/- 0.3 pmol/L, n = 12), breast milk (6.8 +/- 1.6 pmol/L, n = 16), and saliva (2.0 +/- 0.2 pmol/L, n = 15) obtained from healthy subjects. Chromatography studies verify the identity of endothelin. Fast protein liquid chromatography (FPLC) showed one peak in the normal plasma extract, three peaks in the plasma extracts from diabetic patients and patients undergoing maintenance hemodialysis, three peaks in the urine extract, four peaks in the milk extract, and five peaks in the saliva extract. When the materials eluting in the void volume on FPLC of urine and saliva extracts were loaded onto a Sephadex G-25 column, the ir-ET was eluted in a higher molecular weight region. Incubation of endothelin-1, endothelin-2, and endothelin-3 in urine for 5 h showed that the total amount of ir-ET decreased to less than 30% of the initial levels, suggesting that endothelins are very unstable in urine.
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PMID:Immunoreactive endothelin in human plasma, urine, milk, and saliva. 172 88

Release of endothelin-1 (ET-1) from the mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were measured by radioimmunoassay after purification using immunoaffinity column. The identity of ET-1 in perfusate was established using reversed-phase high-performance liquid chromatography. The mesenteric arteries from 5- to 6- and 9- to 10-week-old SHR released a significantly higher level (mean +/- SEM) of ET-1 (32.8 +/- 2.8 and 47.5 +/- 4.1 pg/h, respectively) than WKY age-matched rats (23.4 +/- 2.1 and 34.8 +/- 3.7, respectively). There was an age-related increase in ET-1 release in both groups of rats. Though the SHR studied were in the hypertensive stage, the present results suggest that locally produced ET-1 may contribute to the development of hypertension independent of the plasma levels.
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PMID:Endothelin-1 release from mesenteric arteries of spontaneously hypertensive rats. 172 94


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